Bone loss together with osteoarthritis (see project ZOl AG 00290- 03 LCP entitled "Osteoarthritis and Aging") is one of the two principal age related changes of the human skeleton. Even though these changes are considered universal phenomena inherent to aging, they may result in incapacitating ailments. Advanced bone loss may result in osteoporosis and frequent bone fractures. At some time during the fourth decade of life, the human skeleton begins to lose bone. That is, bone mass decreases in relation to bone volume. In tabular bones, cortical bone is resorbed from the endosteal surface. Because of the thinning of the cortical bone shell, bones lose their mechanical integrity and fracture more readily. The trabecular bone mass of the vertebral column also decreases with age. The vertebral plates decrease in density, loss resistance to vertical compression stress and are more vulnerable to vertebral collapse. Vertebral compression fractures and fractures of the femoral neck are the most serious consequences of bone loss. The following skeletal sites are involved in the present study: hand- wrist, ulna and radius, vertebral column and the proximal femur (trochanter, neck and Ward's triangle). This project deals with the epidemiological, genetic, cross-sectional, longitudinal and biochemical aspects of bone loss (1) among the participants of the Baltimore Longitudinal Study. (2) in a sample of normal adult Guamanians (Chamorros). (3) in genetic isolates in Croatian Islands of Yugoslavia, (4) among patients afflicted with Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex of Guam, (5) in long distance runners and relatively inactive normal controls, and (6) in rats and other animals.